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11508 Background: An ISG, GEIS, FSG and PSG randomized trial on 3 cycles of neoadjuvant epirubicine+ifosfamide (EI) versus a histology-tailored (HT) regimen in selected localized high-risk STS showed some superiority of EI in all histologies with the exception of Myxoid Liposarcoma (MLPS) where EI and HT regimens seemed equivalent (J Clin Oncol 2020; 38:2178-86). This MLPS cohort was expanded with the aim to assess the non-inferiority of the HT regimen compared to EI. Methods: This was a multicenter European randomized trial comparing EI versus a HT regimen. Patients (pts) had localized high-risk (grade = 3; size >5 cm; deeply seated) undifferentiated pleomorphic sarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, synovial sarcoma or MLPS of extremities or trunk wall. Primary end-point was Disease Free Survival (DFS). Secondary end-point was Overall Survival (OS). The MLPS cohort was expanded after the results of the 3rd interim analysis (Lancet Oncol 2017; 18:812-22) in order to reject the hypothesis that HT regimen trabectedin is associated with a HR of relapse = 1.25 with a non-inferiority design. To this aim, a Bayesian monitoring approach was used until the probability that the true HR is higher than 1.25 was greater than 80% or smaller than 5%. Results: From May 2011 to June 2020, 101 pts affected by high-risk MLPS were randomized, 56 to EI and 45 to HT regimen. The median follow-up was 66 months (IQ range 37-89). Median size was 107 mm (IQ range 84-143), 108 mm (IQ range 86-150) in the EI and 106 mm (IQ range75-135) in the HT arm. The DFS and OS probabilities at 60 months were 0.86 and 0.73 (HR:0.60; 95%CI: 0.24-1.46; log rank p = 0.26 for DFS) and 0.88 and 0.90 (HR:1.20; 95%CI:0.37-3.93; log rank p = 0.77 for OS), in the HT and EI arm, respectively. 5-yr observed and Sarculator-predicted OS were 0.89 (95% CI 0.82-0.97) and 0.80 in all patients (p = 0.020), 0.90 (95% CI 0.81-1.00) and 0.79 in the EI arm (p = 0.049) and 0.88 (95% CI 0.77-1.00) and 0.81 in the HT arm (p = 0.204) respectively. Conclusions: In the expanded cohort of MLPS, the HT neoadjuvant therapy trabectedin was not inferior to EI. While survival in both arms was better than predicted by Sarculator, it is left to understand whether this patient population, who had on average a lower Sarculator-predicted risk of death compared with the rest of the trial population, may benefit from a neoadjuvant therapy. Clinical trial information: NCT01710176.

11575 Background: To further explore the activity of T as second/further line treatment in retroperitoneal leiomyosarcoma (LMS) and well differentiated/dedifferentiated liposarcoma (LPS). The primary endpoint of the study was the growth modulation rate (GMR) defined as the ratio between the time to progression under T (TTP) and during previous chemotherapy treatment (TTP-1). The secondary end-points were objective response rate as per RECIST and PFS. Methods: This was a multicenter, single-arm Phase 2 study, conducted in 20 Italian centers. Patients with locally relapsed or metastatic disease, already treated with one or more previous systemic treatments with anthracyclines and/or ifosfamide, were enrolled. T was administered at a dose of 1.3-1.5 mg/mq with a top dose of 2.6 mg per cycle. T was administered as a 24h continuous infusion until progressive disease, major toxicity, patient’s intolerance or medical decision. As per protocol, patients were considered responders if the GMR was > 1.33, non-responders if < 0.75 and neither if 0.76-1.32. Eighty evaluable patients were needed to detect an odds of trabectedin response ≥ 2.5, corresponding to 71.4% of patients with a GMR > 1.33 (80% power, one-sided alpha 2.5%). Results: From August 2014 to February 2019, 104 patients were registered and 91 were evaluable for the primary endpoint (32 pts with LMS and 59 with LPS). Overall, the median number of cycles received was 6.0 (q1-q3 3.0-12.0), the main reason for treatment discontinuation was disease progression in 72% of patients, followed by medical decision (8%). The median TTP was 6.0 months (6.2 and 6.0 for LMS and LPS), while the median TTP-1 was 7.5 months (8.1 and 6.4 for LMS and LPS). Thirty three patients (52% 95%CI: 36-58, p = 0.674, odds of response = 1.1) had a GMR > 1.33 (LMS: 46%, 95%CI 26-67,odds = 0.85; LPS 56%, 95%CI 40-72, odds = 1.3).Overall, response rate (CR+PR) was 16% (24% for LMS and 12% for LPS). Overall, in LPS we observed 15/47 patients with GMR < 0.5 and 15/47 with GMR > 2. Among LMS patients, 9/26 had a GMR < 0.5 and 10/26 > 2. Between LPS six patients had a GMR > 5. Previous treatment had been based on anthracyclines and/or ifosfamide in 85% of patients (91% in LPS population). Conclusions: While the primary end point of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with T in comparison to previous therapy (GMR < 0.5 or > 2, the latter including some pts with a long TTP with T). Efforts are ongoing to assess the pathologic counterparts of such discrepancies. T seems to be selectively active in poorly understood subgroups, with a pattern of activity distinct from other available agents. Clinical trial information: 2012-005428-14.

11003 Background: SFT is a rare soft tissue tumor. In advanced SFT chemotherapy has only limited activity. With the rationale of a rich vascular network & VEGF (tumor cells and endothelium) and VEGFR1/2 (endothelial cells) expression in SFT, we designed an international, single-arm phase II trial to test pazopanib (P) in advanced SFT. Clinical and preclinical evidence suggesting that antiangiogenics was less effective in more aggressive compared with less aggressive SFT (Stacchiotti et al), led us to conduct the trial on two different cohorts: typical and malignant (M)/dedifferentiated (DD) SFT. Here we present the outcome of the latter cohort. Methods: Most relevant inclusion criteria were: unresectable or metastatic, M/DD SFT confirmed by central pathologic review with evidence of STAT6 (IHC and /or FISH or RT-PCR), ≥ 18 years, ECOG 0-2, progressive and measurable disease. Main endpoint was response rate (RR) according Choi criteria. Central radiological assessment was mandatory. P was administered at 800 mg/d continuously until progression or toxicity. Results: From June 2014 to November 2016, 34 patients (pts) were enrolled with a median age of 61 y (23-87). Median tumor size and mitosis at diagnosis were 77 mm and 8x10 HPF. Most relevant grade 3-4 toxicity were neutropenia (9%) and hypertension (12%). At the time of the present analysis, 31 pts are evaluable for response. RR according to Choi and RECIST were: PR 16 (52%), SD 7 (22%), PD 8 (26%) and PR 1 (3%), SD 19 (61%), PD 11 (35%) respectively. With a median follow-up of 15 months, the median PFS was 5.53 months (4.24-6.82), while 72% survived at 18 months. Size > 5 cm, mitosis > 8 and DD subtype showed significantly worse PFS. The 18-month OS was 90% for those with SD and PR and 25% for PD according to Choi (p < 0.001), while 94% for SD and PR and 45% for PD according RECIST (p = 0.002). In multivariate analysis, only Choi was an independent prognostic factor for OS with PD showing a HR of 11.9 (2.3-63.1), p = 0.003 for the risk of death. Conclusions: Pazopanib showed activity in malignant SFT. Choi criteria exhibited a more accurate assessment of response than RECIST. Clinical trial information: NCT02066285.

11042Background: The reported response rate to chemotherapy (CT) in SFT is low both with anthracycline-based regimens ( ≤ 20%) and with trabectedin ( < 10%). DTIC can be active. We report on the co...